GPR119激动剂MBX-2982的小鼠药效学及大鼠体内药动学研究

发布时间：2018-04-16 00:35

本文选题：MBX- + GPR激动剂　；参考：《中国药学杂志》2015年01期

【摘要】：目的研究GPR119激动剂MBX-2982对小鼠糖耐量的影响以及对KK-Ay小鼠各项指标的影响,评价其降糖效果,并进一步评价其在大鼠体内的吸收情况。方法以KM小鼠评价MBX-2982单次给药后对其糖耐量的影响;以KK-Ay小鼠体重、空腹血糖、糖耐量、甘油三酯、血清胰岛素为评价指标考察其药效情况;以大鼠进行不同剂量下的药动学实验,考察灌胃给予MBX-2982混悬液和溶液的吸收情况。结果正常小鼠糖耐量实验中,灌胃给予3、10、30 mg·kg-1的MBX-2982后均可降低各时间点的血糖值。MBX-2982以10、30 mg·kg-1剂量连续给药4周后,能显著降低KK-Ay小鼠的空腹血糖、降低血清甘油三酯、增加血清胰岛素水平,30 mg·kg-1剂量还能显著降低糖耐量实验中血糖曲线下面积。大鼠0.4%羧甲基纤维素混悬液4mg·kg-1灌胃给药后的绝对生物利用度约为35.2%,而二甲基亚砜-蓖麻油-生理盐水=1∶1∶8溶液4 mg·kg-1灌胃给药后的绝对生物利用度为98.2%。结论动物实验结果显示,MBX-2982作为GPR119激动剂有很好的降糖效果,其全溶溶液的口服生物利用度远高于混悬液,接近于100%。
[Abstract]:Objective to study the effects of GPR119 agonist MBX-2982 on glucose tolerance in mice and on the indexes of KK-Ay mice, and to evaluate its hypoglycemic effect and its absorption in rats.Methods the effects of single dose of MBX-2982 on glucose tolerance in km mice, body weight, fasting blood glucose, glucose tolerance, triglyceride and serum insulin in KK-Ay mice were evaluated.The absorption of MBX-2982 suspension and solution by intragastric administration of MBX-2982 was investigated by pharmacokinetic experiments at different doses in rats.Results in the glucose tolerance test of normal mice, the blood glucose value of each time point could be decreased by intragastric administration of MBX-2982 at 30 mg / kg-1. MBX-2982 could significantly reduce the fasting blood glucose and serum triglyceride of KK-Ay mice after 4 weeks of continuous administration of 10 ~ 30 mg kg-1.Increasing the serum insulin level (30 mg kg-1) also significantly decreased the area under the blood glucose curve in glucose tolerance test.The absolute bioavailability of 4mg kg-1 suspension of 0.4% carboxymethyl cellulose was about 35.2g, while the absolute bioavailability of dimethyl sulfoxide (DMSO) -castor oil-physiological saline (1: 1: 8) solution (4 mg kg-1) was 98.2%.Conclusion the results of animal experiments showed that MBX-2982 had a good hypoglycemic effect as a GPR119 agonist, and the oral bioavailability of the whole solution was much higher than that of the suspension solution, which was close to 100g.
【作者单位】：中国医科大学附属第一医院药学部;中国医科大学药学院;沈阳中海生物技术开发有限公司;
【分类号】：R965

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